This is a continuation of the collaborative program with Dr. Chiaho Shih of Dept. of Biochemistry and Biophysics, University of Pennsylvania, Dr. Leo Lee of the Frederick Cancer Research Facility and Dr. Yuan Devires of Div. Biochemistry and Biophysics, FDA. Dr. Shih has developed a rat hepatoma cell line which produced human hepatitis B virus (HBV) by transfusion with cloned HBV DNA. This cell line, Q7 21-HBV, was provided to us for collaborative research projects. Since this was the first time that HBV could be propagated in a non-human cell line, it provided the understanding that the species barrier for this virus lay on the attachment and/or penetration of the virus to hepatocyte. We have attempted to use this in vitro model system to search for HBV inhibitory drugs and to explore the potential treatment scheme. We have designed and synthesized many anti-sense oligodeoxynucleotides in either unmodified or phosphorothiolated form. We have standardized an in vitro assay system to test these anti-sense DNA. Preliminary results showed that most oligodeoxynucleotides are too toxic to cell culture and only one of the modified forms possessed inhibitory effect. Additional drugs will be searched and explored in this system.